Ageing and remyelination failure in people with multiple sclerosis

Abstract

One of the most promising strategies to delay, prevent, or reverse disability progression in multiple sclerosis (MS) is enhancing endogenous remyelination. While preclinical research has established a strong connection between ageing and remyelination failure, evidence for this same link in people with MS remains less secure. As clinical trials for remyelinating therapies progress, clarifying this relationship is essential. A deeper understanding could guide the selection of therapeutic candidates, refine patient selection, and optimise the timing of treatment delivery. In this review, we describe the available evidence that has investigated the impact of age on remyelination in people with MS. We categorise these into pathological, imaging and clinical studies. We explore the challenges in measuring remyelination in humans and determine the implications for the connection between remyelination and age. Current evidence suggests that there is reduced capacity for remyelination with advancing age in people with MS. However, these findings are at times inconsistent and the precise contribution of ageing to remyelination failure is unclear. There does not appear to be an age cut-off beyond which remyelination is not possible, as there are pathological data supporting remyelination occurring, to some extent, across all ages. Interestingly, the impact of age may vary by lesion location. Further targeted research, specifically exploring the relationship between ageing and remyelination, is needed. With emerging evidence that ageing processes might be malleable, we conclude that targeting the biology of ageing might also be an important strategy to therapeutically enhance remyelination.